This invention relates to pharmaceutical formulations. In particular, it relates to pharmaceutical formulations of the semi-synthetic cephalosporin antibiotic known as ceftazidime.
The antibiotic ceftazidime is described by O. Callahan, et al., in U.S. Pat. No. 4,258,041 and is chemically named (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetami do]-3-(1-pyridiniummethyl)-3-cephem-4-carboxylate. Ceftazidime has been obtained as a crystalline pentahydrate, which is a useful form for pharmaceutical formulations of the antibiotic. Ceftazidime pentahydrate is described by Brodie, et al., in U.S. Pat. No. 4,329,453. It has been found that formulations of ceftazidime pentahydrate can degrade, particularly when stressed at higher than room temperatures, and that the degradation can lead to the development of high molecular weight polymer in the formulation. Degradation leading to polymers having a molecular weight of about 10,000 or greater have been observed to impart toxicity to the formulation. Further, such degradation diminishes the pharmaceutical elegance of the formulations and is to be avoided for that reason alone.
The formulations of ceftazidime pentahydrate provided by this invention suppress the formation of polymer having a molecular weight greater than about 10,000, even upon stress of the formulation, and, thus, provide a more pharmaceutically elegant product for administration.